Recurrent aphthous ulcers (RAU) or oral canker sores are the most common oral lesions afflicting humans. Studies have shown such ulcers affect 18% to 50% of the general population. As the name suggests, RAU lesions tend to recur in susceptible patients, often lasting for weeks. These lesions can be characterized as necrotizing ulcerations of oral mucosal tissue which are located on soft, non-keratinized mucosa. The lesions are painful, affect nutritional intake, and disrupt oral hygiene. They lead commonly to secondary infections by opportunistic organisms and sometimes result in scarring.
The etiology of RAU has been linked to several causative factors including allergies, trauma, stress, autoimmune dysfunction, nutritional deficiencies, microbial infection, hormonal changes, and systemic disease. However, several studies have shown that whatever the specific etiology in a particular patient, the clinical manifestations of RAU are due to an altered immune response. Immunosuppressive steroids such as triamcinolone acetonide have been found to be effective in the treatment of RAU. A problem with steroidal therapy for RAU however, is that administration in large doses or over extended periods can cause adrenal suppression and atrophy. The dosage necessary for steroidal therapy to have therapeutic effect for RAU can be lessened, thereby decreasing the opportunity and magnitude of harmful side effects, if the therapy is applied topically rather than systemically. Furthermore, treatment periods necessary to achieve the desired therapeutic effect can be shortened if the form of the product encourages patient compliance in applying the medication on a prescribed schedule.
Several methods of treatment for aphthous ulcers have been explored, including oral tape adhesives and bioadhesive compositions. For instance, U.S. Pat. Nos. 4,517,173 to Kizawa et al., 4,765,983 to Takawanagi et al., 4,772,470 to Inoue et al., and 4,876,092 to Mizobuchi et al. all disclose the use of oral tape adhesives. Through clinical experience, Applicants have discovered that oral mucosal tapes have very poor patient compliance. The tapes are awkward to apply, easily dislodged, and are a source of constant irritation and discomfort when applied to the oral mucosa.
Other attempts at delivery of medication to the oral mucosa have included bioadhesive compositions based primarily on organic cellulose, such as disclosed in U.S. Pat. No. Re.33,093 issued to Schiraldi et al., and polycarbophils disclosed in U.S. Pat. No. 4,615,697 issued to Robinson. The major disadvantages of such compositions is that they are aqueous systems which do not provide as rapid symptomatic relief as the compositions of the present invention, and which are relatively easily removed from the oral mucosa by the flow of saliva.
The present invention overcomes the foregoing problems by combining the therapeutic effect of steroids to counter the dysfunctional immune response associated with RAU, with a local anesthetic to provide immediate symptomatic relief, in an organic base material which provides optimal delivery of the active medications to the lesions. The base material of the present invention is an ointment having wet adherent properties which is not readily displaced from the oral mucosa even in the presence of saliva, and which allows the active medications to remain concentrated and localized over the RAU lesions for an extended treatment period.
It is accordingly an object of the present invention to provide a therapeutic composition for effective local delivery of medicaments to mucosal surfaces. It is a further object of this invention to provide a therapeutic composition for the treatment of recurrent aphthous ulcers by the sustained local delivery of immunosuppressive agents. It is a further object of this invention to provide a composition for the topical treatment of RAU by efficiently delivering therapeutic levels of immunosuppressive agents to lesions by means of an ointment having wet adherent properties which is not easily removed from oral mucosa in the presence of saliva. A still further object of this invention is to provide a therapeutic composition which encourages patient compliance by providing rapid symptomatic relief to the pain of aphthous ulcers. Other objects, features and advantages of this invention will be apparent to those skilled in the art from the ensuing description and examples.